Somebody asked me how many Bruce Springsteen concerts I have been to, and I really couldn’t answer with any certainty. My friend Dick answered “50 or 60” for himself, but I know I haven’t been to that many. Maybe 15-20. And if this was the last time I got to see Bruce perform, I’d die a happy Springsteen fan.

For some reason, Bruce and the band have some type of special connection to Sweden. Not sure if it’s because of his liberal politics and humanitarianism, the images of summer fun that come through many of his songs, or because Clarence “Big Man” Clemons’ first wife was from Goteborg, but something brings out the best in the band when they are there. The most famous of Goteborg shows happened in 1985, when the crowd got into it so much that stress fractures formed by the crowd stomping and dancing forced the reconstruction of Ullevi stadium. Always a great show, always a great crowd, happy Swedes moving to every word and sax solo. And that was certainly true on this chilly 27 June evening.

Bruce surely doesn’t play with the same gut wrenching, unadulterated passion or near anger that we remember — just go on YouTube and pick out anything from the late 70’s early 80’s for comparison. Now its more like he’s having fun out there with his family and friends, playing what he likes and enjoying the gig. Hard to blame him, he’s played these songs for so many years, so many 3-4 hour concerts, its unreasonable to expect him to keep that passionate edge into his 60’s. And his voice no longer reaches those beautiful deep baritones that you could hear on Thunder Road or Backstreets.  But every now and then you get that sincere, authentic sharing of thoughts and feelings that raises your awareness of where you are, where you’ve been, and a little of what it all really means. And you stand up a little straighter, nod your head in agreement, and dance along with 80,000 of your closest Swedish friends.

I’m still holding out for one last show at Red Rocks, maybe with a pared down band and the rock/gospel/soul feeling that he has shown glimpses of.  But if it doesn’t happen, I’ll still have the last words from this last show ringing in my ears.

  “if you can’t make it, stay hard, stay hungry, stay alive! And meet me in the dreams of this hard land…”

I recently participated in a panel at a local conference on healthcare and life science investing. The moderator asked me a question about how I thought the drug development process could be changed to make it more efficient, cost effective, quicker, and more like the technology development process. At the time I was a bit surprised by the question, given the complexity of the problem. Though I have thought a lot about this, like anyone in the biotech industry, I could only laugh and mumble something about Big Data saving the day.

Since this blog provides me an opportunity to develop ideas and put them down on paper (or screen) without the risk of sounding foolish to a large audience, I will expound on two ideas that I have been thinking about for quite some time: 1) reducing the high level of efficacy evidence needed in drug approvals and, and 2) reducing the impact the placebo effect has on drug testing.

FDA role in drug development. The FDA was formed in 1906 with the mission to monitor the safety levels of food and drugs, as well as the “standard of strength, quality, and purity” of drugs. In 1938 its charter was revised to mandate premarket safety reviews of all new drugs, monitoring of false therapeutic claims, and expansion of manufacturing inspections. Its role has evolved over the years to act as the gatekeeper for new therapeutics that are being developed for the market. My question is why the FDA should require such a high level of efficacy evidence before some level of approval, and whether they instead should be focused on making sure that only drugs with minimal safety risk and appropriate side effects are allowed to come to market. If a drug is shown to have a reasonable safety profile, relevant to the disease state to be treated, would it not be reasonable to allow a company or institution to market that as a product? In this day of rapid and thorough communication, with information moving freely and quickly from the research world to patients, physicians, and providers, most companies will be required by the market to provide some evidence of therapeutic effect in treating a condition. It takes many patients use before we really know how well a drug works, and in many instances evidence of therapeutic usefulness, or lack thereof, aren’t evident until several years in the hands of physicians and patients.

My opinion is based on the assumption that no drugs are without safety risk, and all will produce some side effects. The significance of these are dependent upon the disease state they are trying to treat. Chemotherapeutic drugs are some of the most prescribed drugs in the history of medicine, yet the side effects and safety profile of these are terrible. We allow it because the disease being treated is essentially terminal, and so patients accept the risk associated with the therapeutic in order to have a chance to live longer, or with better quality of life. Drugs to alleviate pain are also highly prescribed, and in this case the people taking the drugs will usually tolerate some low level side effects, particularly if they are dose dependent. The FDA allows these drugs on the market, despite their high level of addictive effect, because of the condition and lack of available alternatives. Alzheimers drugs are another example where a strong safety profile, and some reasonable rationale and data suggesting efficacy, should be enough to allow doctors and patients to make their own decisions on prescription and usage.

Thus, the first job of the FDA is to judge whether drugs that have shown some level of evidence to help patients have side effects that are serious enough to prevent it from going to market. Or whether there are certain populations of patients that might be at higher risk of suffering significant problems from the side effects of the drug.

Once the decision on safety has been made, whether binary or relative to patient state, then the FDA should require some level of experimental data in humans that shows a positive therapeutic effect in a population of patients. Positive data from a Phase II trial, for example could be sufficient. In reality, no reimbursement institution will approve paying for a drug that lacks efficacy data, so product developers will need to plan for clinical trials, just as they do now. In the meantime, however, why not allow all experimental drugs and devices, which have demonstrated sufficient safety data, be allowed to be prescribed by physicians? My belief is that this would lead us away from a series of placebo controlled trials, and into more comparative efficacy trials, which would hold more meaning for physicians, patients, and providers. I will take of the question of placebo controlled trials in a later blog.

Getting on that plane to start the journey to Europe, the experience is one of subdued stimulation. This sensation started in the vivid awareness of my youth, when I was definitely more wide-eyed and inexperienced than I am today, but the feeling persists even into my sixth decade. You’re not walking onto a plane, you’re walking onto a time and space capsule, ready to transport you to another world. Once I get on that transport machine, I have a definite change in attitude and disposition, my sense of adventure is aroused. No longer bound by a list of objectives, I now have the time and space to relax, read, watch movies, or just think. I do what I want to for the approximately 15 hours it takes to complete the trip. Time slows down in that flying tube, and the mind takes a break from the constant focus on things to do.  That is, at least until boredom starts to set in after sitting in an 18 inch seat with no space for the legs to fit, and I start feeling a bit queasy from breathing stale air, and ready to taste some real food.

Walking off the plane, you sense a feeling of relief from that cramped space, and hope you have everything you intended to take with you. Immediately you start to hear the strange languages and sounds, workers using segways and mini-bikes to move themselves around the airport, and always offers to purchase some type of European goods — chocolates, alcohol, perfumes — at duty free rates, whatever that is. You get to follow whatever strange customs are followed by the country you have landed in. I am always attracted to the people swirling sugar into their cappuccinos, and amazed at the number of people that are drinking large beers or glasses of wine when we land in Europe. Not quite sure where that comes from, as I rarely see anyone drinking anything before lunchtime, at least in northern Europe.

The provincial fashion sense is also something that usually is striking. Whether getting off the plane in Britain, Sverige, Italia, Espana, or Poland, the clothing and dress of the people always seems somewhat provocative, and fun. It makes the t-shirts and jeans that we are used to seeing in the US seem pretty trite and uninspired, although I would also say that the t-shirts and jeans mode correctly reflects the attitudes and sensibilities of our own country and culture.

The flight home, curiously, I experience as a reverse of the flight out. I usually walk onto the plane having assimilated somewhat into the culture. The customs and fashions no longer feel so unusual, and in fact may be integrated into my being by now. The relaxed mood encouraged by the sensual experience of being in that different culture allows me to settle into the seat with a low awareness of my current list of objectives and action items. I generally try to hold onto that feeling as long as I can, and usually succeed, at least through the plane ride and for the 48 hours thereafter. After that, it’s back to the coal mine, turning big rocks into little rocks, and trying to work through that endless list of things needed to get done.

Anyone who has worked with startup companies knows that it generally takes twice as long and double the dollars to get a company off the ground. In the case of Oberon FMR, now called Nutrinsic, it took seven full years.

The company was started with a concept and some nice experiments done in Norway, not quite at the “business plan on a napkin” level.    While doing a postdoctoral fellowship in Norway, Colorado School of Mines graduate Andy Logan came upon a method to take waste water streams from food processing plants and turn them into high quality protein production processes. The resulting product turned out to be a source of protein that was ideal for fish consumption. As you can see in the graph below, the amount of fish eaten in the world continues to increase about 8% per year, while the amount of wild catch fish leveled off around 1990. Since then, that shortfall has been filled by the aquaculture industry, still in its infancy. Unfortunately, it generally takes several pounds of small fish (herring, anchovies, etc) to make one pound of farmed fish, obviously an unsustainable model. Hence, the need for Profloc, which is the brand name for the Nutrinsic fish meal replacement protein.

Founder Andy Logan brought in fellow engineer Seth Terry as a partner, and the two founders brought in Randy Swenson as a business guy to help get the company going. HCV helped the team write the first full business plan, which attracted the first lead investor in Aquacopia, a VC firm that focuses on aquaculture innovation. Two CEO changes and one global financial implosion later, the company finally broke ground this week on its first US plant in Trenton, Ohio, with Miller Coors as its first partner.

Saturday night at the board dinner we ate some fantastic Cobia, a species of fish being farmed at one of Aquacopia’s portfolio companies in Panama. It was delicious, and a sign of the development of the aquaculture industry. I look forward to eating more Cobia, fed with the sustainable fish meal replacement Profloc in the near future. Congratulations to the team at Nutrinsic! Perseverance is a large part of success in the startup world.

05 February, 2014

I am diving into the blogosphere in order to keep a promise to myself. I’m not expecting any fame, glory, or money from this, but I hope some of my thoughts will be interesting, and relevant enough to influence some of the readers who wander into this space.

The title of the blogsite, The Promise, holds several layers of meaning. There is the personal promise, often between people, which can be either spoken or unspoken. Good examples of this are the marriage vows, or the employment contract. There are the promises within society, which underlie much of our culture. An example of this in the news today is the assumed promise that society makes to us, that if you work hard and persevere you will have an opportunity to improve your quality of life. Another one is the promise underlying the payment of taxes, in exchange for which the government agrees to help take care of you in case you become sick, old, or poor. Finally, there are promises in the spiritual and theological realm. I’ll leave that one for a later blog, as it could take up a lot of words. There is also the promise one sees in individuals or teams, in which big expectations are placed. Or, in the case of the Denver Broncos, misplaced.

In my next entry I will give a bit more about my background, which is admittedly a bit eclectic. In my 57 years I have been a research scientist, a head brewer at a microbrewery, and lately a venture capital investor in early stage biotechnology and medical device companies. I will draw on the experiences I have accumulated throughout my life, and will often refer back to this notion of the Promise, which encompasses the faith that we all need to have in order to not only keep going in life, but to keep creating in the world. If we lose faith in that Promise, then our belief in the world and the people around us becomes shaken, and that is when we lose our desire and will to contribute, and be a part of, all the important interactions going on around us.

I made a promise to myself when I lived in England thirty years ago, as a masters student at the University of Sussex. At the time I had just gone through two of the best years of my life, and the combination of life’s growth, new found friends, the European way of life, and some fine Burton beers inspired me with ideas that I thought would make an interesting book. I’m not sure that I’ll ever get to writing that book, but maybe this place will serve the purpose. Sometimes a promise half kept is enough. We shall see what we shall see.